Today ChemSpider (www.chemspider.com) is one of the community’s primary online resources for chemists. Now hosting over 28 million unique chemical compounds linked to over 400 data sources, ChemSpider offers its users a structure centric platform facilitating access to publications and patents, experimental and predicted property data, spectral data and many other forms of data and information that can benefit a chemist. ChemSpider is a crowdsourcing platform allowing the community to contribute data directly to the database by allowing the deposition and sharing of structure data, properties, spectra and reaction syntheses. The crowdsourcing also allows for the annotation and curation of existing data thereby allowing the community to assist in the much-needed curation and validation of chemistry data on the internet. This work is imperative in order to provide the chemistry underpinnings to semantic web projects such as Open PHACTS (www.openphacts.org) of which Merck is sure to benefit when it is released to the community. This presentation will provide an overview of the ChemSpider platform and will also examine the challenges of dealing with heterogeneous data quality when attempting to provide a rich resource of data for the community. If you use the internet to research chemistry based data this presentation will be an essential guide to how to source high quality data.

1. Chemistry Online – The Vision and
Challenges Associated With Building
the ChemSpider Resource for Chemists
Antony Williams
Merck, October 2012

2. We Have …Too Much Data!!!

3. It is so difficult to navigate…
IP?
What’s the
structure?
Are they in
our file?
What’s
similar?
What’s the
Pharmacology target?
data?
Known
Pathways?
Competitors?
Working On
Connections Now?
to disease?
Expressed in
right cell type?

5. The World of Online Chemistry
 Property databases
 Compound aggregators
 Screening assay results
 Scientific publications
 Encyclopedic articles (Wikipedia)
 Metabolic pathway databases
 ADME/Tox data – eTOX for example
 Blogs/Wikis and Open Notebook Science
 Contributing Open Source code to projects

6. PubChem

7. ChEMBL

8. Collaborative Knowledge Management

9. Data on the Web

10. RSC’s ChemSpider

11. We Want to Answer Questions
 Questions a chemist might ask…
 What is the melting point of n-heptanol?
 What is the chemical structure of Xanax?
 Chemically, what is phenolphthalein?
 What are the stereocenters of cholesterol?
 Where can I find publications about xylene?
 What are the different trade names for Ketoconazole?
 What is the NMR spectrum of Aspirin?
 What are the safety handling issues for Thymol Blue?

12. Available Information…
 Linked to vendors, safety data, toxicity, metabolism

13. Available Information….

14. Crowdsourced “Annotations”
 Users can add
 Descriptions/Syntheses/Commentaries
 Links to PubMed articles
 Links to articles via DOIs
 Add spectral data
 Add Crystallographic Information Files
 Add photos
 Add MP3 files
 Add Videos

16. ChemSpider : Spectra Linked

17. Spectra Linked

18. Spectra Linked

19. Chemistry Data online is messy
 We have inherited errors
 All public compound databases, including ours,
have errors
 “Incorrect” structures – assertions, timelines etc
 “Incorrect” names associated with structures
 Properties
 Links
 Publications
 ENORMOUS CHALLENGE

20. What could create change?
 Harvard Business Review (2010)
“One change would make a substantial
difference [to drug R&D]: the creation of
agreed-upon standards for digitally
representing drug assets.”
Consider drug structures ONLY…

21. The Structure of Vitamin K?

22. MeSH
 A lipid cofactor that is required for normal blood
clotting. Several forms of vitamin K have been
identified: VITAMIN K 1 (phytomenadione)
derived from plants, VITAMIN K 2 (menaquinone)
from bacteria, and synthetic naphthoquinone
provitamins, VITAMIN K 3 (menadione). Vitamin K 3
provitamins, after being alkylated in vivo, exhibit the
antifibrinolytic activity of vitamin K. Green leafy
vegetables, liver, cheese, butter, and egg yolk are
good sources of vitamin K

23. The Structure of Vitamin K1?

24. What is the Structure of Vitamin K1?

25. CAS’s Common Chemistry

26. Wikipedia

29. ChEBI – Manual Curation

33. “2-methyl-3-(3,7,11,15-tetramethylhexadec-2-
enyl)naphthalene-1,4-dione”
 Variants of systematic names on PubChem
 2-methyl-3-[(E,7R,11R)-3,7,11,15-tetramethyl
 2-methyl-3-[(E,7S,11R)-3,7,11,15-tetramethyl
 2-methyl-3-[(E,7R,11S)-3,7,11,15-tetramethyl
 2-methyl-3-[(E,7S,11S)-3,7,11,15-tetramethyl
 2-methyl-3-[(E,11S)-3,7,11,15-tetramethyl
 2-methyl-3-[(E)-3,7,11,15-tetramethyl
 2-methyl-3-(3,7,11,15-tetramethyl
 2-methyl-3-[(E)-3,7,11,15-tetramethyl

34. Chemistry on The Internet Is Messy

35. It’s Methane…

36. What’s Methane?

37. What’s Methane?

38. What ELSE is Methane???

40. EPA’s DailyMed

41. EPA’s DailyMed

42. EPA’s DailyMed

43. With Great Fanfare…

44. NPC Browser http://tripod.nih.gov/npc/

45. NPC Browser http://tripod.nih.gov/npc/

47. The EXPERTS must get it right?!

48. Wikipedia, C&E News, PubChem
C&E News (from ACS)

49. People Use Trusted Resources…

50. Earlier this month…

51. Stop Whining – Fix it

52. Crowdsourced Curation
 Crowd-sourced curation: identify/tag errors, edit
names, synonyms, identify records to deprecate

53. Search “Vitamin H”

54. “Curate” Identifiers

55. “Curate” Identifiers

56. “Curate” Identifiers

57. What is the outcome of this???
 IF we can get the community to help clean up the
internet of chemistry then we have:
 High quality online reference resources
 Freely available reference data
 Ongoing iterative curation – how many
chemical structures are “reworked”
 And what is the value of “curated chemical
dictionaries???”

58. Successful Semantic Markup
Depends on Dictionaries

59. Dictionaries Enhance Publications

60. I want to know about “Vincristine”

61. Vincristine Identifiers

62. Vincristine: Patents
Linked by Name

63. Vincristine: Articles
Linked by Name

64. What are the names for this
compound just in patents????

65. A disambiguation NIGHTMARE!

66. Ambiguity in Identifiers

67. Crowdsourcing Works
 >130 people have deposited data and
participated in data curation
 Different level curators check each other
 More curators and depositors encouraged!
28 million chemicals is a long list…

68. ChemSpider for Analytical Sciences
 ChemSpider is being developed with the intention of
 Being the world’s richest resource of freely
accessible curated analytical data
 As a platform for structure verification and
dereplication
 To provide access to supporting prediction
algorithms

69. Spectral Uploading
 Locate the structure of interest and deposit
spectrum
 Supported formats: JCAMP, PDF

70. Spectral Uploading
 Various types of NMR spectra supported

71. Regular Updates

72. Multiple Spectra for One Structure

73. ChemSpider ID 24528095 H1 NMR

74. ChemSpider ID 24528095 C13 NMR

75. ChemSpider ID 24528095 HHCOSY

76. ChemSpider ID 24528095 HSQC

77. ChemSpider ID 24528095 HMBC

78. Full C13 assignment uploaded

79. Available Spectra
http://www.chemspider.com/spectra.aspx

80. How do these data get curated?
 Every spectrum can be commented on
 Incorrect spectra have been annotated and
curated by users…
 But curation through gaming is also possible…

81. Web Services

82. www.SpectralGame.com
http://www.jcheminf.com/content/1/1/9

83. Spectral Game

84. Increasing Complexity

85. Spectral Game

86. Reversed Spectrum

87. True Curation of Data

88. SpectralGame in the hand

89. In progress…
 Storage and display of ASSIGNED spectra

90. Mass Spec Analysis

91. ChemSpider Interface

93. Tinuvin 328

94. Position sorted by references

95. Position 1 only

96. Web Services

97. Web Services Open Up Collaboration
 Agilent, Bruker, Waters and Thermo all use our
web-based services for compound lookup
 Many academic sites integrating directly –
metabonomics, name lookup, semantic markup

98. Where do data come from?
 ChemSpider users deposit data
 Some contributions from NIST
 Chemical vendors are starting to provide data.
Synthonix are one of our major contributors
(www.synthonix.com)

99. Commercial Database Access
 Recently deposited to ChemSpider
 EPA/NIST IR Database >5000 spectra
 Presently under development
 NIST MS database >200,000 MS spectra

100. Where next with Analytical Support?
 PharmaSea project for the identification of natural
products – dereplication approaches
 Use mass spectrometry searches of natural
product slices to identify
 Pre-fragment compounds and develop
searches
 Dereplication using NMR data
 NMR features
 Predicted spectra and “Verification approaches”

101. NMRShiftDB: http://www.ebi.ac.uk/nmrshiftdb/

103. NMR Prediction

104. NMRShiftDB Data Review
• High quality NMR shift set of ca. 100,000 shifts
• Derived prediction algorithms give very similar
performance statistics to commercial algorithms

105. Crowdsourcing Chemical Synthesis
 How much data generated in a lab, that COULD
go public, is lost forever?

106. Crowdsourcing Chemical Synthesis
 How much data generated in a lab, that COULD
go public, is lost forever?
 Public Domain reference databases of value?
 Properties
 Spectra
 CIFs
 Images
 Syntheses

107. An Adventure into the World of Small
but significant contribution..

108. ChemSpider SyntheticPages

109. Micropublishing with Peer Review
(a chemical synthesis blog?)

110. Multi-Step Synthesis

111. Interactive Data

112. MOBILE Structure Database Lookup

113. It is so difficult to navigate…
IP?
What’s the
structure?
Are they in
our file?
What’s
similar?
What’s the
Pharmacology target?
data?
Known
Pathways?
Competitors?
Working On
Connections Now?
to disease?
Expressed in
right cell type?

114. Open PHACTS Project
 Develop a set of robust standards…
 Implement the standards in a semantic integration hub
 Deliver services to support drug discovery programs in
pharma and public domain
 22 partners, 8 pharmaceutical companies, 3 biotechs
 36 months project – goes live next month
Guiding principle is open access, open usage, open source
- Key to standards adoption -

115. The Future
Internet Data
Small organic molecules Commercial Software
Undefined materials Pre-competitive Data
Organometallics Open Science
Nanomaterials Open Data
Polymers Publishers
Minerals Educators
Particle bound Open Databases
Links to Biologicals Chemical Vendors

116. The Future of Chemistry on the Web?
 Public compound databases federate & build
a linked environment of validated data!
 Data validation needs are not ignored
 Publishers layer on information to make
publications discoverable
 Public-Private databases can be linked
 Open Data proliferate
 The “Semantic Web” in action

117. Can Merck Contribute to this Project?
 Do you have any data that you can release into the
public domain?
 Measured property data
 How many “common” spectra are thrown away?
 How many syntheses are published and locked
behind paywalls?
(www.chemspider.com/reactions)
 Can your scientists contribute annotations and
curations if they use ChemSpider?
 Is the challenge of Legal Clearance too big?

118. Thank you
Email: williamsa@rsc.org
Twitter: ChemConnector
Blog: www.chemspider.com/blog
Personal Blog: www.chemconnector.com
SLIDES: www.slideshare.net/AntonyWilliams